When the diet provides more than enough protein, weight maintenance is determined primarily by interactions between intake and oxidation of carbohydrates and fats. Since the body's glycogen reserves contain only about 1/100 of the energy stored as body fat, metabolic regulation and endocrine signals are poised to give priority to the adjustment of carbohydrate oxidation to carbohydrate intake. Furthermore, we found in ad libitum fed mice that the adjustment of food intake is more responsive to deviations from the carbohydrate than from the fat balance. Yet weight maintenance requires as well that fat oxidation be commensurate with fat intake. On diets with a substantial fat content, decreases in the rate within which glycogen reserves are kept an/or increases in the size of the adipose tissue mass are necessary to raise circulating free fatty acid levels enough to bring about the oxidation of a metabolic fuel mix with a fat-to-carbohydrate ratio equivalent to that of the diet. We will therefore determine how alterations of the relative proportions of different types of fats and carbohydrates in the diet modify the body composition for which the plateau of weight maintenance is reached in ad libitum fed mice. The reversibility of the dietary leverage will be studied by sequential assessment of the body fat content using body density measurements in lean and obese strains of mice. By measuring daily nutrient intake and the 24 hour respiratory exchange, we will determine the oxidation of carbohydrate and of fat, and their daily balances over many consecutive days. This allows for the first time to assess how changes in energy expenditure and in food intake, and of variations in the RQ contribute to the "corrective responses" which bring about maintenance of body weight, by compensating for temporary deviations from the glycogen, fate and energy balances. The influence thereon of hormones (e.g. corticosterone, thyroxin), of exercise, and of weight reducing drugs will be studied. By providing animals with diets inducing high rates of de novo lipogenesis, or by exposing them to variable degrees of cold, we will attempt to demonstrate that increases in energy expenditure do not necessarily lead to a reduction i body weight, as generally believed. The effect of spontaneous physical activity on energy expenditure will be measured, in order, among other, to obtain further in vivo data on differences in "net ATP yields" when carbohydrate or fate is oxidized. The main goals of the proposed investigations are (a) to characterize the impact of the diet's fat content and of the nature of the carbohydrates consumed on steady-state body composition under ad libitum feeding conditions, and (b) to delineate the relative importance of deviations from the carbohydrate, fat or energy balances int he spontaneous regulation of food intake. In time this may contribute to explain why a reduction in the diet's fat content facilitates weight maintenance at a lower level of adiposity, particularly individuals who are not physically active.